Bone replacement material comprising crystalline and X-ray amorphous phases

ABSTRACT

The present invention relates to an X-ray amorphous-crystalline material with high solubility which can be used as a bioactive bone replacement material and as a substrate material in biotechnology. The new material comprising crystalline and X-ray amorphous phases is characterized in that according to  31 P-NMR measurements, it contains Q 0 -groups of orthophosphate and Q 1 -groups of diphosphate, the ortho-phosphates or Q 0 -groups making up 70 to 99.9% by weight relative to the total phosphorus content of the finished material and the diphosphates or Q 1 -groups making up 0.1 to 30% by weight relative to the total phosphorus content of the finished material, and that according to X-ray diffractometric measurements and relative to the total weight of the finished material, 30 to 99.9% by weight of a main crystal phase consisting of Ca 2 K 1−x Na 1+x (PO 4 ) 2 , where x=0.1 to 0.9, is contained in the bone replacement material and 0.1 to 20% by weight of a substance selected from the group consisting of Na 2 CaP 2 O 7 , K 2 CaP 2 O 7 , Ca 2 P 2 O 7  and mixtures thereof is contained as a secondary crystal phase, the X-ray amorphous phases contained besides the main crystal phase jointly making up 0.1 to 70% by weight relative to the total weight of the finished material.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates to an X-ray amorphous-crystallinematerial with high solubility which can be used both as a bioactive bonereplacement material, e.g. in the form of a coating applied ontometallic prosthesis sticks by thermal spraying or by rf sputtering, andas a substrate material in biotechnology, especially in tissueengineering, e.g. in the form of a ceramic sheet or of a compact orporous, i.e. spongiosa-like, scaffold-like, moulded body. The inventionalso relates to a manufacturing method.

[0003] 1. Description of the Related Art

[0004] In principle, inorganic materials which are easily resorbed areknown. Materials which are specifically used as bioactive bonereplacement materials and dissolve quickly have also been described inthe relevant literature. For example, there have been numerouspublications dedicated to the successful clinical use of ceramicmaterials the main crystal phases of which are alpha- or beta-tricalciumphosphate (TCP). In addition, there have been comparative analyses ofthese two TCP phases using animal tests. It is known from EP 237043 thatgranulated materials made of alpha-TCP contain dicalcium phosphate ontheir surface, whose solubility was higher than that of the purealpha-PCT core material, especially in the initial phase following animplantation.

[0005] The chemical solubility of the aforesaid granulated materials wassurpassed by other bioactive materials based on calcium phosphates whichin addition contain oxides of potassium, sodium, magnesium and/orsilicon (EP 541564 B1) and the glassy-crystalline material of which isbased on the following main crystal phases: Phase X, rhenanite, phaseaccording to Ando (Phase A) and/or mixed crystals derived from theaforesaid phases.

SUMMARY OF THE INVENTION

[0006] The object of the invention is to provide an X-rayamorphous-crystalline material which enables a substantially directjoining of bones without connective tissue and/or the ex vivocultivation of bone cells, and which dissolves in contact with bonetissue, and which at the same time has high solubilities which areadjustable in a more precise manner and, in the case of compositematerials, coefficients of expansion adapted to certain steels. Anotherobject of the invention is to develop a method for manufacturing theaforesaid material as well as manufacturing aids.

[0007] According to the invention, the bone replacement materialconsists of crystalline and X-ray amorphous phases and contains:

[0008] according to ³¹P-NMR measurements, Q₀-groups of orthophosphateand Q₁-groups of diphosphate, the orthophosphates or Q₀-groups making up70 to 99.9% by weight relative to the total phosphorus content of thefinished material and the diphosphates or Q₁-groups making up 0.1 to 30%by weight relative to the total phosphorus content of the finishedmaterial, and

[0009] wherein according to X-ray diffractometric measurements andrelative to the total weight of the finished material, 30 to 99.9% byweight of a main crystal phase consisting of Ca₂K_(1−x)Na_(1+x)(PO₄)₂,where x=0.1 to 0.9, is contained and 0.1 to 20% by weight of a substanceselected from the group consisting of Na₂CaP₂O₇, K₂CaP₂O₇, Ca₂P₂O₇ andmixtures thereof is contained as a secondary crystal phase, and

[0010] wherein the X-ray amorphous phases contained besides the maincrystal phase jointly make up 0.1 to 70% by weight relative to the totalweight of the finished material.

[0011] The secondary crystal phase is preferably made up ofdiphosphates, but one or more of the substances NaPO₃, KPO₃ and mixturesthereof can also be contained, the chain phosphates NaPO₃ and KPO₃ beingdetectable as Q₂-groups according to ³¹P-NMR measurements. The chainphosphates are contained in an amount ranging between 0.1 and 10% byweight, preferably 0.1 and 4% by weight.

[0012] Further, the secondary phase may contain a silicate phase in anamount ranging up to 6% by weight, corresponding to the SiO₂ content.

[0013] The aforesaid main crystal phase and the constituents of thesecondary crystal phase may contain magnesium in an amount ranging up to10% by weight, calculated as MgO and relative to the weight of thefinished material.

[0014] The orthophosphate phase represented by Q₀-groups preferablymakes up 75 to 99% by weight, particularly 78 to 95% by weight.

[0015] The diphosphate phase represented by Q₁-groups preferably makesup 1 to 22% by weight, particularly 5 to 16% by weight.

[0016] The composition of the X-ray amorphous-crystalline material withhigh solubility which is based on CaO, P₂O₅, Na₂O, K₂O, MgO andoptionally SiO₂ ranges between (in % by weight):

[0017] 30 and 55 P₂O₅; 5 and 50 CaO;

[0018] 1 and 20 Na₂O; 0.5 and 20 K₂O;

[0019] 0 and 13 MgO; 0 and 10 SiO₂;

[0020] MgO or SiO₂ or a mixture thereof making up at least 1% by weight.

[0021] A preferred X-ray amorphous-crystalline material is composed asfollows (in % by weight): 35 to 48 P₂O₅, 28 to 38 CaO, 2.5 to 15 Na₂O,1.5 to 18 K₂O, 0.1 to 4 MgO, 0.0 to 3 SiO₂. A special preferredembodiment contains 40 to 52 P₂O₅, 28 to 33 CaO, 8.5 to 13 Na₂O, 9.5 to15 K₂O, 1.5 to 3 MgO, 0.1 to 4 SiO₂.

[0022] In general, the term “X-ray amorphous-crystalline” material usedherein cannot be clearly defined. “X-ray amorphous” as used hereinrefers to a material whose structure cannot be determined using standardXRD (X-ray diffractometry). The undetectable areas can be very smallorganized areas (micro-crystalline) as well as statistically unorganizedareas. Unlike XRD, the ³¹P-NMR results can be used to detect theexistence of any crystalline phase. Therefore quantitative estimatesbased on NMR and XRD results can be rather different. In the presentcase, this phenomenon seems to be particularly true of the diphosphateand chain phosphate contents; as a rule, ³¹P-NMR measurements yieldconsiderably higher contents than XRD. In some cases, no contents at allare found using XRD. This impressively shows why ³¹P-NMR measurementsare an essential prerequisite for characterizing and finallymanufacturing the materials according to the invention. XRD measuringwas made with PW 1710, Philipps, NL (CuK radiation).

[0023] Both crystalline and X-ray amorphous phases can therefore beprovided in a thoroughly mixed state. It is of no importance for thepresent invention whether one phase is located adjacent to the other orone phase encloses the other. The term “main crystal phase” as usedherein refers to a crystalline phase which is detected using X-raydiffraction and is contained in at least twice the amount of a secondaryphase, concentrations of 20% and below, preferably below 15% by weight,being referred to as secondary phases.

[0024] For the sake of clarity, it must be pointed out that“Ca₂KNa(PO₄)₂” can certainly be identified as main crystal phase.However, there are shifts of intensity in the individual compositions,which may be rather substantial in some cases, due to the varying ratioof sodium to potassium or the inclusion of other ions (e.g. Mg²⁺ or SiO₄⁴⁻) so that the formula “Ca₂K_(1−x)Na_(1+x)(PO₄)₂, where x=0.1-0.9” isto be used. Higher Na contents are preferred, e.g. x=0.2-0.9.

[0025] Surprisingly, solubility has been found to be particularly highif the product obtained by the melting process contains in particularcrystalline diphosphates such as Na₂CaP₂O₇, K₂CaP₂O₇ and/or Ca₂P₂O₇ oreven a majority of X-ray amorphous di-phosphates besides the maincrystal phases and X-ray amorphous orthophosphates. Further, it wassurprisingly found that the aforesaid statement can be clearlyquantified using ³¹P-NMR measurements.

[0026] The ³¹P-NMR measurements, which were carried out using asuperconductive Fourier NMR spectrometer known as Avance DMX400 WB andmanufactured by Bruker BioSpin GmbH (Germany), showed that the materialconsists of 70 to 99.9% by weight orthophosphate of calcium and in somecases orthophosphate of sodium, potassium and magnesium, wherein theaforesaid orthophosphate content is determined using ³¹P-NMRmeasurements of Q0-groups and refers to crystalline and/or X-rayamorphous material in its entirety. In addition, 0.1 to 30% by weightdiphosphate of calcium and in some cases diphosphate of sodium,potassium and magnesium was found, wherein the aforesaid diphosphatecontent can be reliably determined using ³¹P-NMR measurements(Q₁-groups) and refers to crystalline and/or X-ray amorphous material inits entirety.

[0027] Further, it is advantageous that 0.1 to 10% by weight chainphosphate consisting of sodium phosphate or potassium phosphate or bothbe contained, wherein this chain phosphate content represented byQ₂-groups is reliably determined by means of ³¹P-NMR measurements andrefers in particular to amorphous and, as the case may be, crystallinematerial in its entirety. In addition, 0.1 to 10% by weight of asilicate phase may be contained, depending upon the amount of SiO₂added. Moreover, Ca₅Na₂(PO₄)₄ may be contained, although this is notpreferred.

[0028] Further, it has surprisingly been found that the desired effect,i.e. a considerably improved solubility, is brought about by thepresence of diphosphates and/or chain phosphates, preferablydiphosphates, as will be demonstrated in Example 3.

[0029] The diphosphate contents result from a comparatively highphosphate content relative to the other constituents. The aforesaidphosphate content could also be the reason why the compositionsaccording to the invention melt very easily yielding a rather fluid meltcompared to known resorbable materials. Such a low-viscosity melt hasthe advantage that it has a better processability. That is the case fora frit of the melt or a direct blowing of the melt etc.

[0030] Further, it has surprisingly been found that due to the presenceof di-phosphates the ion discharge behaviour of the material (the X-rayamorphous-crystalline material), which in the beginning shows a strongalkaline reaction, changes more pronouncedly towards physiological pHvalues (7.4) than that of materials not containing diphosphate, providedthe material was stored in deionized water. Due to this shift in pHvalues, the material is also of interest to biotechnology, in particularto tissue engineering.

[0031] The aforesaid feature can be enhanced by boiling a (compact oropen-pore) moulded body in deionized water (37-90° C.) thus leaching itssurface so that the material or moulded body treated in this way hasconsiderably lower pH values once the treatment is finished. Thisphenomenon could be put down to a reduction of the alkaline cations inthe area near the surface of the material. The aforesaid process can beaccelerated by boiling the material in a reactor, advantageously at apressure of up to 10 bars. Such an embodiment of the invention ispreferred.

[0032] It is an advantageous feature of the material according to theinvention that its solubility can be adjusted within relatively wideranges, depending upon the selected composition; specifically, the totalsolubility can range between 30 and 500 μg/mg relative to the startingmaterial if the test is carried out in 0.2M TRIS-HCl buffer solution atpH=7.4, T=37° C. using a grain size fraction of 315-400 μm, the durationof the test being 120 h and the ratio of weighed-in sample to buffersolution being 50 mg to 40 ml.

[0033] The material according to the invention is manufactured bycombining the substances suitable for preparing the mixture to bemelted, their concentrations (relative to the total weight of thematerial) being in the range of 30-55% by weight CaO, 35-50% by weightP₂O₅, 1-20% by weight Na₂O, 0.5-20% by weight K₂O and 0.1-5% by wieghtMgO and optionally up to 5% by weight SiO₂, and melting them at between1,550 and 1,650° C. in a suitable crucible material, e.g. consisting ofa Pt/Rh alloy, using multistage thermal treatment programmes includingholding stages in the range between 200 and 1,500° C., namely 1-2 h at350-400° C., 750-850° C. and 950-1,050° C., e.g. 1 h at 400, 800 and1,000° C. respectively. The melt is poured, preferably following aholding time of between 10 and 60 min, and once the mass has solidifiedit is cooled down to room temperature in air (spontaneous cooling) or ina cooling furnace using a temperature-controlled cooling process, e.g.at a rate of 1 to 20 degrees/min, depending upon its intended use. Themelt can also be blown thus directly forming the melt into sphericalgranules. In both cases, a spontaneous crystallization process takesplace while the melt cools down. The mixture to be melted may compriseoxides, carbonates, hydrogen phosphates and/or ortho-phosphoric acid.The ³¹P-NMR measurements yield different spectra allowing conclusions asto the raw materials used or indicating small amounts of iron oxides ormanganese oxides contained therein. Preferred melting temperatures rangebetween 1,590 and 1,650° C.

[0034] Once the material has cooled down, it is granulated and used as abone replacement material, but it can e.g. also be ground, mixed withcommonly used sintering aids and be isostatically pressed into mouldedbodies in order to obtain a densely fired ceramic body after sintering.In general, the sintering temperatures range between 900 and 1,200° C.

[0035] Alternatively, the material manufactured according to theinvention can e.g. be ground, mixed with commonly used sintering aidsand processed into a slurry which is then applied onto a polyurethanesponge and sintered in several sintering stages at such hightemperatures that the polyurethane sponge and the sintering aids areburnt completely and a spongiosa-like body is obtained the maincrystalline constituents of which areCa₂K_(x−1)Na_(x+1)(PO₄)₂(x=0.1-0.9) and Na₂CaP₂O₇, K₂CaP₂O₇, Ca₂P₂O₇and/or mixed crystals in between these phases.

[0036] In a preferred embodiment of the invention, some of the rawmaterials used are melted separately in order to obtain a glass whichacts as a sintering aid and can be used for the production of thespongiosa-like bodies in a particularly advantageous manner. Theaforesaid glass is ground and can be added to the slurry consisting ofthe material according to the invention which has been ground followingthe melting and cooling processes and then processed into a slurry. Theglass melted separately can be added to the slurry in an amount rangingbetween 0.5 and 15, preferably 4-8% by weight, relative to the amount ofsolid matter contained therein, providing, however, that the individualcomponents are not contained in the composition in larger amounts thanthose indicated in the invention. Such a glass can in particular beproduced on the basis of SiO₂, MgO and Na₂O.

[0037] In this embodiment, the sintering process leads to a very solidstructure of the moulded body, whereas parts of the moulded body maycrumble away if all components are melted together and then sintered.The glass melted separately has a grain size D₅₀ ranging between 0.7 and7 μm when being added to the ground material, whose grain size issimilar or larger.

[0038] Therefore the present invention also relates to a glass used as asintering aid for resorbable materials containing calcium phosphateswith the exception of tri-calcium phosphate, which glass ischaracterized by the following chemical composition in % by weight:SiO₂: 68-78, preferably 73-78, particularly 74-75 MgO: 5-12, preferably8-11, particularly 8.5-10 Na₂O: 12-27, preferably 12-19, particularly14.5-17 K₂O: 0-22, preferably 0-5 P₂O₅: 0-20, preferably 0-10.

[0039] Another processing option consists in grinding the material,adding commonly used sintering aids and processing the slurry obtainedin this way into a sheet which has an open-pore structure once thefiring process is finished.

[0040] Advantageously, the material according to the invention can alsobe provided in combination with a metallic implant surface. Thematerial's coefficient of expansion ranges between 12 and 18×10⁻⁶ K⁻¹,measured using a dilatometer (silica glass pushrod dilatometer(Kieselglas-Schubstangen-Dilatometer) manufactured by Netzsch GerätebauGmbH, Germany), so that an adaption to known steels, e.g.chromium-cobalt-molybdenum steels having similar coefficients ofexpansion, is particular advantageous.

[0041] The present invention also relates to the use of the X-rayamorphous-crystalline material according to the invention formanufacturing granulated materials, ceramic bodies or ceramic sheets.

[0042] The invention will hereinafter be explained by means of examples.All percentages are by weight unless indicated otherwise.

BRIEF DESCRIPTION OF THE DRAWINGS

[0043]FIG. 1: shows ³¹P-MAS-NMR spectra of the materials GA 1, GA 2 andGA 3 according to the invention, whose composition corresponds toExample 1 and whose phases correspond to Example 5 (MAS=Magic AngleSpinning);

[0044]FIG. 2: shows the ³¹P-MAS-NMR spectra of the materials GA 4 and GA5 according to the invention, whose composition corresponds to Example 2and whose phases correspond to Example 5.

DETAILED DESCRIPTION OF THE INVENTION EXAMPLE 1

[0045] The following materials were synthesized according to the amountsindicated in the table in % by weight: Code CaO MgO P₂O₅ Na₂O K₂O SiO₂GA 1 30.67 2.45 43.14 9.42 14.32 0.00 GA 2 29.92 2.39 44.53 9.19 13.970.00 GA 3 29.21 2.33 45.85 8.97 13.64 0.00

[0046] To facilitate understanding, this melting process can also bedescribed as follows: GA 1; GA 2(=GA 1+2.5% P₂O₅); GA 3(=GA 1+5% P₂O₅).

[0047] The mixtures to be melted were weighed in as follows: 85% CaCO₃MgO H₃PO₄ Na₂CO₃ K₂CO₃ SiO₂ Code In g in g in ml in g in g in g GA 154.4 2.45 41.48 16.11 21.01 0 GA 2 53.40 2.39 42.82 15.72 20.50 0 GA 352.13 2.33 44.09 15.34 20.01 0

[0048] First, the components comprising calcium, magnesium, sodium andpotassium and optionally silicon, are weighed in. Once the weighing-inprocess is finished, each mixture is mixed in a tumbling mixer for onehour. Then the 85% ortho-phosphoric acid is added to the mixture, themixture is thoroughly ground in a mortar, stirred and dried at 100° C.for one hour, ground in a mortar again and stored once more in a dryingchamber at 100° C. for one hour. Subsequently, the mixture was onceagain ground in a mortar, filled into a Pt/Rh crucible and heated up to400° C., at which temperature it was held for one hour, then heated upto 800° C., at which temperature it was again held for one hour, andthen heated up to 1,000° C., at which temperature it was also held forone hour. The sinter cake produced in this way was cooled in air andground in a mortar again in order to make it more homogeneous. Thepretreated mixture was then filled into a platinum crucible and heatedup to 1,600° C. in a melting furnace. Once the aforesaid temperature hadbeen reached, the melt was maintained at this temperature for half anhour. The low-viscosity, homogeneous melts were then poured onto a steelplate and pressed using a second steel plate so that a salt-likesolidified plate was obtained. The crystallization taking place duringthis stage gives an opaque, white colour to the bodies obtained by themelting process.

EXAMPLE 2

[0049] Following the same production procedure as described in Example1, i.e. preparing a mixture of calcium carbonate, sodium carbonate,potassium carbonate and orthophosphoric acid, the following compositionswere synthesized according to the amounts indicated in the table in % byweight: Code CaO MgO P₂0₅ Na₂0 K₂O SiO₂ GA 4 31.54 1.19 42.37 9.17 13.951.78 GA 5 30.79 1.16 43.74 8.95 13.62 1.73

[0050] Low-viscosity melts were obtained for all compositions, whichmelts spontaneously crystallized when being cooled. The crystallizationproducts had a white colour.

EXAMPLE 3

[0051] Another manufacturing option consists, inter alia, in that theamount of phosphorus or phosphate may be brought in by means of acalcium carrier, either in its entirety or, as in the present example,in part. The following composition was synthesized according to theamounts indicated in the table in % by weight: Code CaO MgO P₂0₅ Na₂0K₂O SiO₂ GA 1 30.67 2.45 43.14 9.42 14.32 0.00

[0052] The mixture to be melted was weighed in as follows: Magnesiumhydroxide 85% CaCO₃ carbonate H₃PO₄ Na₂CO₃ K₂CO₃ CaHPO₄ Code in g in gin ml in g in g in g GA 1 0.00 5.13 4.25 16.11 21.00 74.43

[0053] The mixture to be melted was weighed in according to the amountsindicated above, mixed in a tumbling mixer for one hour, phosphoric acidwas added, the mixture was dried at 100° C. for one hour, cooled in airand ground in a mortar. The mixture obtained in this way was filled intoa platinum crucible, placed in a furnace which had been preheated to450° C. and held at this temperature for 6 hours, and was then placed ina furnace which had been preheated to 800° C. and held at thistemperature for 16 hours. The crucible was taken out and the furnace waspreheated to 950° C. The crucible was then held in the furnace preheatedto 950° C. for 6 hours. Subsequently, the sample was heated up to 1,600°C. and held at this temperature for half an hour. The low-viscosity,homogeneous melt was then poured onto a steel plate and pressed using asecond steel plate so that a salt-like solidified plate was obtained.The crystallization taking place during this stage gives an opaque,white colour to the bodies obtained by the melting process. Adiscoloration can be observed, depending upon the CaHPO₄ component usedand undesirable amounts of iron and/or manganese contained therein.

[0054] It is also possible to directly quench the melt in a water bathonce the melting process (1,600° C., 0.5 h) is finished (fritting) inorder to facilitate the further comminution of the product obtained bythe melting process if it is to be further processed in the form of aslurry.

EXAMPLE 4

[0055] The samples according to Example 1 and selected samples accordingto Example 2 (see the following table) were used to produce granulatedmaterials having a grain size ranging between 315 μm and 400 μm in orderto determine solubility. The solvent used was 0.2M TRIS-HCI buffersolution with a pH value of 7.4 and at a temperature of 37° C. Theanalyzed amount was 50 mg using 40 ml solvent. The granulated materialswere stored at 37° C. for a period of 120 h. Subsequently, the totalsolubility was determined by determining the individual ions (of Ca, Mg,P, Na, K) in the solution by means of an ICP measurement: SolubilityCode [μg/mg] GA 1 95 ± 8 GA 2 134 ± 16 GA 3 221 ± 22 GA 4 90 ± 8 GA 5152 ± 10

EXAMPLE 5

[0056]³¹P-MAS-NMR spectra of the samples according to Example 1 andExample 2 were recorded with a waiting time of 120 s between theindividual pulses. The samples rotated at a speed of 12.5 kHz.

[0057] The quantitative composition of the samples as regards theirphosphate content is indicated in the following table: Chain phosphateOrthophosphate Diphosphate content content content [predominantly[(PO₄)³⁻] [(P₂O₇)²⁻] (PO₃)¹⁻ Code in % in % in % GA 1 99.5-96 0.5-4 — GA2 88 12 — GA 3 79 21 — GA 4 95  5 — GA 5 89 11 —

[0058] The range indicated for the composition GA 1 is based on theanalysis of three batches one of which was synthesized according to themanufacturing method described in Example 3, whereas only one sample wasanalysed for each of the other compositions.

EXAMPLE 6

[0059] In the zirconium oxide bowl (250 ml) of a planetary mill, theproduct obtained by the melting process having a composition accordingto code GA 1 was ground two times for 20 min. The result is shown in thefollowing table. D₅₀ value Code [in μm] GA 1 6.50

EXAMPLE 7

[0060] The ground GA 1 sample according to Example 6 is to be processedinto “scaffolds”. For this purpose, a slurry was produced by combining100 g of the ground material with 45 g of a mixture consisting of 90%polyethylene glycol and 10% of a commercially available surface-activeagent and adding 5 ml isopropyl alcohol. The slurry obtained in this wayis applied onto open-pore PUR sponges (PUR=polyurethane) whose porosityranges between 80 and 20 ppi (pores per inch) by repeatedly immersingand squeezing the sponges, dried overnight in a drying chamber at 120°C. and then slowly heated up to 1,000° C. at a rate of 10° C. perminute. The result is a spongiosa-like material the structure of whichresembles that of the sponge used, while the PUR sponge has burntcompletely.

EXAMPLE 8

[0061] In order to further increase the strength of the spongiosa-likebodies, 3% by weight of a previously produced glass having a chemicalcomposition of (in % by weight) 74.97 SiO₂, 9.22 MgO and 15.81 Na₂O(melted as 27.04 Na₂CO₃) and a D₅₀ value of 6.56 μm was added to theground material according to GA 1 as a sintering aid. Then a slurry wasproduced by combining 100 g of this powder mixture with 45 g of amixture consisting of 90% polyethylene glycol and 10% of a commerciallyavailable surface-active agent and adding 5 ml isopropyl alcohol. Theslurry obtained in this way is applied onto open-pore PUR sponges whoseporosity ranges between 80 and 20 ppi (pores per inch) by repeatedlyimmersing and squeezing the sponges, dried overnight in a drying chamberat 120° C. and then slowly heated up to 1,000° C. at a rate of 10° C.per minute. The result is a spongiosa-like material the structure ofwhich resembles that of the sponge used, while the PUR sponge has burntcompletely.

EXAMPLE 9

[0062] Samples according to Example 1 and Example 2 were produced andanalyzed by means of ³¹P-NMR measurements. The ³¹P-MAS-NMR spectra wererecorded with a waiting time of 120 s between the individual pulses. Thesamples rotated at a speed of 12.5 kHz.

[0063] As a result, it can be shown that in the case of the samples GA 1through GA 3 (cf. FIG. 1), whose only chemical difference consists inthe increasing phosphate content, this increased phosphate content isreflected in an X-ray amorphous-crystalline diphosphate content in theproduct obtained by the melting process, which also dramaticallyinfluenced solubility (cf. Example 4). This applies analogously to thesamples GA 4 and GA 5 (cf. FIG. 2).

[0064] In the spectra shown in FIG. 1 and FIG. 2, the left (broader)peaks indicate the Q₀-groups and the right (narrower) peaks theQ₁-groups.

EXAMPLE 10

[0065] Material composed according to code GA 1 was freshly ground, 1 gof a grain size fraction <45 μm was added into 100 ml E-pure water, andthe pH value was determined after 1 min and after 72 h. The result was10.55 after one minute and 8.71 after 72 hours, i.e. a clear changetowards physiological conditions could be observed.

EXAMPLE 11

[0066] In order to enhance this effect a priori, the followingexperiment was carried out: A spongiosa-like body was produced accordingto Example 7, i.e. the composition according to code GA 1 was appliedonto a PUR sponge and sintered, except that the sponge used in thepresent example had a porosity of 30 ppi.

[0067] The moulded body obtained in this way, whose outer dimensionswere approx. 11 mm×11 mm×7 mm, was immersed in 100 ml E-pure water andthe pH value was measured after 10 min. The measured value was 9.62.

[0068] Subsequently, the moulded body was eluted in E-pure water at 60°C. and a pressure of 3 bars for one hour. The moulded body was thenrinsed 5 times in 20 ml fresh E-pure water, immersed in 100 ml E-purewater again, and a pH value of 8.83 was measured after 1 hour.

[0069] This demonstrates that the pretreatment of spongiosa-like bodiesdescribed above is a useful activity as products pretreated in this wayhave a lower basicity, which can be advantageous both for implantationin vivo and for tissue engineering ex vivo or in vitro.

EXAMPLE 12

[0070] An important feature with regard to the coating of materials withthe resorbable materials according to the invention consists in that thethermal coefficient of expansion can be varied, bearing in mind e.g.that this coefficient is approx. 8·10⁻⁶K⁻¹ for titanium implants andapprox. 14−16·10⁻⁶ K⁻¹ for Co—Cr—Mo steels (depending upon theconstituents of the alloy). In order to obtain a composite materialwhich is optimally suited to its intended use, the temperature range inwhich the material is applied onto the metallic substrate must becarefully selected as in this way the substrate can be subjected tocompressive strain, i.e. to preheating, in a targeted manner during thecoating process thus obtaining a composite material which in general isregarded as mechanically more stable.

[0071] The following table shows some of the possible variations:CE₃₀₋₁₀₀ CE_(RT**400) CE₅₀₋₄₀₀ Sample (10⁻⁶ K⁻¹) (10⁻⁶ K⁻¹) (10⁻⁶ K⁻¹)GA 1 12.15 14.84 15.14 GA 2 13.64 17.16 17.54 GA 3 13.21 16.99 17.45 GA4 12.51 15.85 16.20 GA 5 13.29 16.69 17.08

[0072] In the table, CE₃₀₋₁₀₀ is the coefficient of expansion between 30and 100° C., CE_(RT**400) is the coefficient of expansion between roomtemperature (25) and 400° C., and and AK₅₀₋₄₀₀ is the coefficient ofexpansion between 50 and 400° C.

1. A bone replacement material comprising crystalline and X-rayamorphous phases, characterized in that a) according to ³¹P-NMRmeasurements, said bone replacement material comprises Q₀-groups oforthophosphate and Q₁-groups of di-phosphate, the orthophosphates orQ₀-groups making up 70 to 99.9% by weight relative to the totalphosphorus content of the finished material and the diphosphates orQ₁-groups making up 0.1 to 30% by weight relative to the totalphosphorus content of the finished material, and b) according to X-raydiffractometric measurements and relative to the total weight of thefinished material, 30 to 99.9% by weight of a main crystal phaseconsisting of Ca₂K_(1−x)Na_(1+x)(PO₄)₂, where x=0.1 to 0.9, is containedin the bone replacement material and 0.1 to 20% by weight of a substanceselected from the group consisting of Na₂CaP₂O₇, K₂CaP₂O₇, Ca₂P₂O₇ andmixtures thereof is contained as a secondary crystal phase, and c) theX-ray amorphous phases contained besides the main crystal phase jointlymake up 0.1 to 70% by weight relative to the total weight of thefinished material.
 2. A bone replacement material comprising crystallineand X-ray amorphous phases, characterized in that a) according to³¹P-NMR measurements, the bone replacement material comprises Q₀-groupsof orthophosphate and Q₁-groups of di-phosphate, the orthophosphates orQ₀-groups making up 70 to 99.9% by weight relative to the totalphosphorus content of the finished material and the diphosphates orQ₁-groups making up 0.1 to 30% by weight relative to the totalphosphorus content of the finished material, and b) according to X-raydiffractometric measurements and relative to the total weight of thefinished material, 30 to 99.9% by weight of a main crystal phaseconsisting of Ca₂K_(1−x)Na_(1+x)(PO₄)₂, where x=0.1 to 0.9, is containedin the bone replacement material and 0.1 to 20% by weight of a substanceselected from the group consisting of Na₂CaP₂O₇, K₂CaP₂O₇, Ca₂P₂O₇ andmixtures thereof is contained as a secondary crystal phase, and c) theX-ray amorphous phases contained besides the main crystal phase jointlymake up 0.1 to 70% by weight relative to the total weight of thefinished material, obtainable by mixing raw materials containing (in %by weight) 25-50 CaO, 1-20 Na₂O, 0.5-20 K₂O, 0-13 MgO and 0-10 SiO₂ andtreating the aforesaid mixture with H₃PO₄ in an amount corresponding to30-55 P₂O₅, SiO₂ or MgO or a mixture thereof making up at least 1% byweight, homogenizing and drying the mixture and subjecting it to astep-by-step thermal treatment lasting 1-2 h at 350-450° C., 750-850° C.and 950-1,050° C. respectively, melting the mixture at between 1,550 and1,650° C., holding it at the melting temperature for between 10 and 60minutes and finally cooling the mixture in a spontaneous ortemperature-controlled manner, grinding it, if necessary, and sinteringit to obtain moulded bodies.
 3. A bone replacement material according toclaim 1, wherein additionally one or more of the chain phosphates NaPO₃,KPO₃ and mixtures thereof are contained in an amount ranging between 0.1and 10% by weight, which chain phosphates can be detected as Q₂-groupsusing ³¹P-NMR measurements.
 4. A bone replacement material according toclaim 1, wherein x ranges between 0.2 and 0.9.
 5. A bone replacementmaterial according to claim 1, wherein the secondary crystal phasecontains a silicate phase corresponding to the SiO₂ content.
 6. A bonereplacement material according to claim 1, wherein additionallymagnesium in an amount ranging up to 10% by weight, calculated as MgOand relative to the weight of the finished material, is contained.
 7. Abone replacement material according to claim 1, wherein theorthophosphate phase represented by Q₀-groups makes up 75 to 99% byweight.
 8. A bone replacement material according to claim 7, wherein theorthophosphate phase represented by Q₀-groups makes up 78 to 95% byweight.
 9. A bone replacement material according to claim 1, wherein thediphosphate phase represented by Q₁-groups makes up 1 to 22% by weight,preferably 5 to 16% by weight.
 10. A bone replacement material accordingto claim 9, wherein the diphosphate phase represented by Q₁-groups makesup 5 to 16% by weight.
 11. A bone replacement material according toclaim 1, wherein the secondary crystal phase makes up 0.1 to 15% byweight.
 12. A bone replacement material according to claim 10, whereinthe secondary crystal phase makes up 1 to 15% by weight.
 13. A bonereplacement material according to claim 1, wherein the total solubilityranges between 30 and 500 μg/mg, relative to the starting material ifthe test is carried out in 0.2M TRIS-HCl buffer solution at pH=7.4,T=37° C. using a grain size fraction of 315-400 μm, the duration of thetest being 120 h and the ratio of weighed-in sample to buffer solutionbeing 50 mg to 40 ml.
 14. A bone replacement material according to claim1, wherein the coefficient of expansion ranges between 12 and 18×10⁻⁶K⁻¹, measured using a dilatometer.
 15. A bone replacement materialaccording to claim 1, wherein the pH value of the surface changes by atleast 0.7 units, preferably at least 1.5 units, towards the neutralpoint within the alkaline range if the material is stored in deionizedwater at room temperature for 72 hours or heated up to 60° C. for 1 hourat a pressure of 1-3 bars and rinsed with deionized water.
 16. A bonereplacement material according to claim 1, wherein said material isprovided in combination with a metallic implant surface.
 17. A bonereplacement material according to claim 1, wherein in the processed,finished state said material consists of (in % by weight): 30 to 55P₂O₅, 25 to 50 CaO, 1 to 20 Na₂O, 0.5 to 20 K₂O, 0 to 13 MgO 0 to 10SiO₂; MgO or SiO₂ or a mixture thereof making up at least 1% by weight.18. A bone replacement material according to claim 17, wherein MgO is inthe range of 1-13% by weight and SiO₂ is in the range of 0.5-5% byweigth; MgO or SiO₂ or a mixture thereof making up at least 1% byweight.
 19. A bone replacement material according to claim 18, whereinsaid material contains 40 to 52 P₂O₅, 28 to 33 CaO, 8.5 to 13 Na₂O, 9.5to 15 K₂O, 1.5 to 3 MgO, 0.1 to 4 SiO₂.
 20. A bone replacement materialaccording to claim 1, wherein said material is provided in the form ofgranulated materials, ceramic bodies or ceramic sheets.
 21. A method formanufacturing a bone replacement material comprising crystalline andX-ray amorphous phases according to claim 1, characterized by mixing rawmaterials containing (in % by weight) 25-50 CaO, 1-20 Na₂O, 0.5-20 K₂O,0-13 MgO and 0-10 SiO₂ and treating the aforesaid mixture with H₃PO₄ inan amount corresponding to 30-55 P₂O₅, MgO or SiO₂ or a mixture thereofmaking up at least 1% by weight, homogenizing and drying the mixture andsubjecting it to a step-by-step thermal treatment lasting 1-2 h at350-450° C., 750-850° C. and 950-1,050° C. respectively, melting themixture at between 1,550 and 1,650° C., holding it at the meltingtemperature for between 10 and 60 minutes and finally cooling themixture in a spontaneous or temperature-controlled manner, grinding it,if necessary, and sintering it to obtain moulded bodies.
 22. A methodaccording to claim 21, wherein the raw materials are divided into twobatches and melted separately, the first batch consisting of a meltedglass comprising 73-78 SiO₂, 8-11 MgO, 8.5-10 Na₂O, 12-19 K₂O and 0-22P₂O₅ (in % by weight), which glass is cooled, ground and added to thesecond batch, i.e. the X-ray amorphous-crystalline material of claim 21,in an amount ranging between 0.1 and 15% by weight and is sinteredjointly with said second batch at 900-1,200° C. to obtain mouldedbodies.
 23. A method according to claim 21, wherein the mixture ismelted at between 1,590 and 1,650° C.
 24. A glass used as a sinteringaid for resorbable materials containing calcium phosphates with theexception of β-tricalcium phosphate, which comprises the followingchemical composition in % by weight: SiO₂: 73-78, MgO: 8-11, Na₂O:12-19, K₂O: 0-22, P₂O: 0-20.
 25. A glass according to claim 24, whichcomprises the following chemical composition in % by weight: SiO₂:74-75; MgO: 8.5-10; Na₂O: 14.5-17; K₂O: 0-5; P₂O₅: 0-10.